Cyto-vaccine of tubercle bacilli



Patented June 2 4, 1 9330 g I JAdOBSi, OMINZ, or RocIiEstnERfNnw from? kq 'cfipjrfnqemn or'T UBnRoLEt BAeILLIl ie prawns; fiPliicajciqnQ Edfeather 39,1923; sraune, 671,390.

- The ,pres'entinvention relates to; a 'eytoirritation; the' rnainmal is'abletoi throw" out 1 Vaccine oftubercle'bacilliiand an' object of at the point-f irritation defensive antiv the 'invention is m rovidemaecine which bodies and enzymes in suflicient quantity'to when injected 111a mammalor ahuman being "otzerconie more or less co'mpletely the toxine Willproduceimmunizingandfltherapeutiereand'irritating substances introducedf These 55 actions Withoutcreating ahscessesj defensive substances produce more or less. *J-In carrying out this l'inyenti'o'n, yirulent complete solution of the Waxy capsule sur cultures oftubefclhadilli aregrownon a rounding the bacteria, and neutralizefmore suitable media, eithers'olidbrlfiuid andfam *or" less completely the toxic protein mole- 10 then carefully and, With' sterile precautions, [cule's present. There is enough of these de- 60 .renioxfedinto a small o 'iiantityfol sterile Tso, fensive substances'left' over sothat, it Withlutioii such'. asj'a 'norrri aline' solution'or dravvngfromthe animal and; injected into sterile Water, to makethein ayailable'forin anotherfanimal, they 'vvillsti'mulate the pro 'jectioninto" an animalijYThesterilitybf.the d utction of "similar protective anti-bodies solution ,is deS ired-in order 'toj ayoid'fconfesp cially since there *is'a 'quantitybf the 65 tan in'ationwith other organisms, While the tubercletoxinev still remaining unacted'on. 'norlnalfsaline solutionis' usedgiin preference Asthe" injection is made subedermally inthe V 't'o' any fther solution;because itf'i's pre'sent iinamni'al; the partwhere the injection" to 7 r in fluidi'portions'of the bodyin considerable be made is clipped, shaved and antiseptifquantity? Thissolutiori enables the deterdallfprepared; and,intheipreparation of "70 i f The suspension oftheliyetubercle bacilli ofayariztble period of fou mining (if the number o'fbacteriaberfcubie fl and yri g and also in th'e makcentinieter ofsolution; so as'to keep a record ingqf the injection, the strictest asceptic pre- 5 of the total'of bacteria injected into the 5m; fcautlon's are followed, to avoid 'cont al'ninau malus'eufor theproduction oftheiv accine. tion W ithfother organisms. {Afterthelapse 1 c i I "to eight Weeks f75 'in'ithe noi'mallsaltIsolutionfisthensubjcted a fluctmtifig=mass develops at the site of" to" a; treatnrie'nt tdkillltheibacillipreferably j ction; I I fl i then evacuated f heatingat"atemperature ofbetween 6Q-to underlstrictjaseptio' and *antiseptieprec'auj "Surfin absolute'fkill i iig" f 'th ifiuberde It hasbeen round that some (5f the tuberd so;

b 'in 'th f' 'pgp si ififBrder tliiiIt Ythe tad-113m" ,thee'nimal are only partially di essential c mponents" "i f'thdhddy of the- 'gfe e t y-defensive ant'iehodiesthrown bacilli' ar'e hammered wt e 1 unggmmm uebythe:apmgal ndth se opari ially digest i when 'ifijec'tdintofafi mu he; defensive ed baol'lhlwl i nj'ected i fa human'bein Y reaction will be a vcomplete9o 6against}all 1 1 *mammal'p duqei rita io -f 'In, 0r'dert o1 5 7 of theele xneiits press-1t i111 the bacteria unffi o dth 's l r t fi n' by the sefundigested"and: Y ehangdsTohiaintaififlie' origifial de feeof *u t d .jlp' n: p l st c r t ll 7 I concentration 0f ,flthe sblution""mainingthe niaterialievacilated-from' the suitable cheinical as;for example; a quantity I ef pi'irefjetlie'r or iethr 'VTapo'r.,]Wlien using Th Gi-liille'dtlillercl bailliiris ether; the ether a dpthe '1'I I I ater ial are then a 't'hefilnorinal"salineflsoliitiofi' is he eeted-thoroughly Iubhed'andmixedto'g h fgiiflt -orde'rit d;niaintain a re rdiblfbw i 45 preferably in one whose 'resi nce td-tliis' gneml m fif f l a s b ridlthegprbd 7 5 f fl 'y' tl e whi m y remin'and whi V 'is' both unnecessary and undesirabldlthefre V 'nioyal oif theethe'r"isobtained byslowe v apo ration; as y heating-the tliin" mogfeneousf J 1 'ifiaterial fat about 30 degrees "Ci 'unt l the 10a ded-td'fiia'ke anima11-is' repamdin-a,gias jmortarwitha1 40"up'theoriginalquanti" thls-tei I for intravenus mass becomes dry. With the end in View of eliminating any lumps inthe material that may'contain any. uneflected waxy substance, the massis thoroughly tritu'rated and is preferably mixed withchemically pure sodium chloride and'sterile' water to produce an emulsion, the sodium chloride accomplishing the breaking up orli gany cellular {elements I which may be present such as leucocytes and interstitial and tissue cells. --Thematerial thus obtained is suitabletOr siIb-dermal ad ministrations. Should a substance be desired administration, furtherurification by extraction with ether and filtration is desirable. Some'sui'table material may -be added for preservative purposes if V I the productis to be ,stored .forhypodermic v use. r

It will be-seen lthattherehas been prov vided'a vaccine which'results from ia cellular reaction on thepartof theinterstit-ual and ftissue cells of theinjected mammal towards "the tubercle bacilli, This material when first withdrawn from the mammal contains tuber cle bacilli invaryingi degrees of disintegration, and also serum and cellular anti-bodies enzymesthat act toproduce disintegra tion "of the tubercle acilli and-neutralization .oi'its' toxines. The whole tubercle bacilli is j contained in .thevaccine in completely dis integrated form,-becauseiof the action of the serum, cellular anti-bodies'and enzymes'of the mammal ,inj e'oted and because ofthe me- 1. The process of making vaccine" of tuberxole bacilli which consists in killing the tubercle bacilli, injecting thekill'ed tubercle ba- -cilli:into an animal, evacuating the ifluctu'atfiil'gmassdeveloped-uponthe animal at the 1-point at injection to iobtain a liquid, and treating the liquidthus-.obtainedto break a down;capsular-structures to render its a-bsorption complete into another mammal in h; tmavb -ni t d. ub ea n lyr-i r i 12.; The process 0f making vaccine o f tu-v bercle baciflli which consists killing the f it;.u -bercle bacilli; injecting the killed tubercle bacilli-into {an animal; evacuating the fluctuatingimass developed upon' the =animalat the point pf injectionfto obtain a liquid, and me .c'hanic ally treating the liquidth ls obtain ejd to breakdown c apsular' structures to render 7 its absonption completeinto another mammal which he ginjccted subsequentlyi 3. The process of making vaccine or tu- V bercle bacilli which consists in killing the tubercle bacilli, injecting the killed tubercle bacilli into an animal, evacuating the fiuctu-- ating mass developed upon the animal at the point of injection to obtain aliquid', and chemically 'and mechanically treating the liquid thus obtained toibreak down capsular structures to renderits "absorption complete into another mammal inwhichit mayjbe'in jected subsequently 4:. The process of making vaccine of tubercle bacilli 'hi'ch consists in killing the V tubercle bacilli, injecting the killed: tubercle bacilli into an animal, evacuating 'fihe' fluctu a-ting mass "developed upon the animalatthe point of ection to :obtain *a 1 liquid, and treating-the liquid thus obtained with ether.

to {break down any remaining capul'ar structures and triturati-ng the liquid mass to break up the remainingcellurlar forms;

5.- The processof making vaccine of 'tu-l I berclea bacilli which consists in killing-the tubercle bacilli, injecting the killed tubercle bacilli into an 'animal', evacuating the fluctuating inass developed upon the animal at the point irofriinjection to obtain a llquid', treating the lieu'iidvtltus obtained withether f to breakdown "any remaining a capsular structuresand triturating the liquidmassto breakup the remaining cellular form, and Y -drying the liquid to produce a dry mass, trit urating thedry massxand miXingthe thorjo-ughly :triturated -mass' with a solution-of "sodium chloride-to produce anemulsion from the trituratedmass, and adding a suitable loo liquid to thetrituratedmass to make a pr-odeuct sui-table for"use hy podermically,

6. The process-of makinga vaccinelof tubercle bacilli which consists in providingvirulent cultures or tubercle bacilliin a sterile saline solution,;heating the solution tokill v the tuberclebacillij, injecting'thekillediltuberclebacillii nto almammal, and evacuating the [fluctuating massdeveloped upon-the mammal toxobtain .a liquid and 'treatin g 1tlre liquid thus obtained to. break down any capjjected'subsequently. 1 r u .o

vaccine of tubercle bacillig obtairied I froma': fluctuating imass developed 1 upon; a a e lmai-n malthrough the-.intjections of killed 111- bercle bacilli in the mammal and containing rtubercle b ac,i=lli in varying degrees of; disin? tegration and ialsolserum and, cellular bodies zsular str-ucturesito render'its absorption-com- 1 b eny' mm i whi t may c and ei aymesvthat'gact to produce disintegra- I tionrof the tubercle ibacilliand.neutralization of its; toxinesgand free from non-absorbabl'e ..tubercle,bacilli.

a 8. vaccine of tubercle, baci lliobtained is I -V from a fluctuatingnmass developed -upona xmammal through the injection o f killed tn bercle-bacilli :andl avingits partially digestv e t ercle 'ba i anab rp ive f m-i 9. A vaccine of .tubercle bacilli'obtained from "a fluctuating mass developed upon the mammal through, the injection of killed tubercle bacilli in the mammal and having its partially digested tubercle bacilli in dis1ntegrated and absorptive-form. .j

10. The process of'making'a vaccine of tubercle bacilli which consists in providing virulent cultures of tubercle bacilli in a sterile normal saline solution, heatin the solution with the tubercle bacilli to ki l'the tubercle bacilli, injecting the solution with the killed tubercle bacilli into a healthy mammal Whose resistance to this type, of infection is high,

7 evacuating the fluctuating mass developed upon the mammal to obtain a liquid containing defensive anti-bodies and partially digested tubercle bacilli, adding ether to the liquid, triturating the same toeliminate all lumps and produce a thin homogeneous, ma-

terial, eliminating the ether by slow evaporation until a dry mass is obtained, triturating the mass to eliminate any lumps, and mixing the dry mass with a solution of sodium chloride to produce an emulsion.

JACOB s; KOMINZ. i 

